Healthy
Conditions
Brief summary
Pharmacodynamic effects on heart rate (HR) at rest and during exercise and on flicker fusion frequency (FFF), FFF method evaluation Safety, tolerability and pharmacokinetics of cilobradine
Interventions
DRUGCilobradine high dose 1
DRUGCilobradine high dose 2
DRUGCilobradine low dose 2
DRUGCilobradine medium dose
DRUGCilobradine low dose 1
DRUGMetoprolol succinate tablets
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* All participants in the study should be healthy males and females. Volunteers will * be 21 to 55 years of age * have a Body Mass Index (BMI) of 19.9 to 29.9 kg/m2 and * have a resting heart rate (HR) (after 10 min. in the supine position) of more than 55 beats per minute (bpm) * Only post-menopausal females, or those who had had a hysterectomy, could participate. All females had to have a negative pregnancy test * In accordance with good clinical practice (GCP) and the local legislation all volunteers had to give their written informed consent prior to admission to the study
Exclusion criteria
* Any finding of the medical examination (including BP, HR and ECG) deviating from normal and of clinical relevance * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Diseases of the central nervous system or psychiatric disorders or neurological disorders * History of relevant orthostatic hypotension, fainting spells or blackouts * Chronic or relevant acute infections * History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the Investigator * Intake of drugs with a long half-life (\> 24 hours) within ten half-lives of the respective drug before enrolment in the study * Use of any drugs which might influence the results of the trial within two weeks prior to administration or during the trial * Participation in another trial with an investigational drug (≤ two months prior to administration or during the trial) * Smoker (\> 10 cigarettes or \> 3 cigars of \> 3 pipes/day) * Inability to refrain from smoking on trial days * Alcohol abuse (\> 60 g/day) * Drug abuse * Blood donation (≥ 100 ml within four weeks prior to administration or during the trial) * Excessive physical activities (within the last week before the study) * Any laboratory value outside the reference range of clinical relevance Not necessarily clinically relevant abnormalities, but specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in heart rate at rest | Pre-dose, up to day 20 after first drug administration |
| Changes in heart rate during exercise | Pre-dose, up to day 20 after first drug administration |
| Changes in flicker fusion frequency test (FFF) | Pre-dose, up to day 20 after first drug administration |
Secondary
| Measure | Time frame |
|---|---|
| Number of patients with clinically relevant changes in 12-lead ECG | Pre-dose, up to 12 days after last drug administration |
| Number of patients with adverse events | Up to 12 days after last drug administration |
| Assessment of global tolerability by the investigator | Up to 12 days after last drug administration |
| Changes in peripheral FFF | Pre-dose, up to day 20 after first drug administration |
| Area under the concentration-time curve of the analytes in plasma (AUC) | Up to day 20 after start of first drug administration |
| Apparent volume of distribution of the analytes during the terminal phase λz following extravascular administration (Vz/F) | Up to day 20 after start of first drug administration |
| Time from dosing to the maximum concentration of the analytes in plasma (tmax) | Up to day 20 after start of first drug administration |
| Terminal half-life of the analytes in plasma (t½) | Up to day 20 after start of first drug administration |
| Mean residence time of the analytes in the body after oral administration (MRTpo) | Up to day 20 after start of first drug administration |
| Total clearance of the analytes in plasma following extravascular administration (CL/F) | Up to day 20 after start of first drug administration |
| Maximum measured concentration of the analytes in plasma (Cmax) | Up to day 20 after start of first drug administration |
| Number of patients with clinically relevant changes in laboratory tests | Pre-dose, up to 12 days after last drug administration |
| Number of patients with clinically relevant changes in vital signs (blood pressure, heart rate) | Pre-dose, up to 12 days after last drug administration |
Outcome results
None listed